Switching antidepressants safely

A rational, evidence-based approach

by ALISON PALKHIVALA  October 2017

The Canadian Network for Mood and Anxiety Treatments (CANMAT) emphasizes the importance of achieving full remission whenever possible in patients with depression. In order to achieve that outcome successfully, a trial of more than one antidepressant is often necessary. For many clinicians, it can be difficult to determine at what point to consider switching antidepressant medication. when a response is not as desired or when tolerability is an issue.

Fortunately, CANMAT offers clear guidelines on when to switch antidepressant therapy. They point out that early response to antidepressants, defined as a 20 to 30% improvement from baseline in a depression rating scale, has been shown to correlate with response and remission at 6 to 12 weeks.

CANMAT recommends that if an antidepressant is not well-tolerated at 2 to 4 weeks, especially if the maximum dose has not yet been reached, switching antidepressants can be considered at this point. If the drug is well-tolerated but efficacy is suboptimal at 2 to 4 weeks, treatment should be optimized. This usually involves increasing the antidepressant dose as well as considering the addition of psychotherapy and/or neurostimulation strategies, if they have not already been initiated. It can also be helpful to revisit the initial diagnosis to ensure nothing was overlooked.1

Identifying the Need to Switch

Patients with an inadequate response to optimized, maximum dose antidepressant therapy at 6 to 12 weeks can be managed either by switching antidepressants or by adding an adjunctive therapy. The decision to switch or add a medication should be individualized. Consider switching over the addition of an adjunctive medication when:
• It is the first antidepressant trial.
• There are poorly tolerated side effects to the initial antidepressant.
• There is no response (< 25% improvement) to the initial antidepressant.
• There is time to wait for a response (i.e., less severe symptomatology, less functional impairment).
• The patient prefers to switch to another antidepressant.1

When switching is deemed to be the best option, taking a rational, evidence-based approach to selecting a new antidepressant can help optimize outcomes. While conclusive data are lacking, some evidence is available to guide clinical decision-making. Evidence for the benefits of switching patients to an antidepressant within the same class versus a different class is equivocal. Thus, CANMAT recommends switching patients to an antidepressant with evidence of better efficacy, regardless of class, as summarized in Table 1.1

Switching Strategies

The four recommended strategies for switching antidepressants are:
1. Direct switch: The current antidepressant is stopped abruptly and the new antidepressant is started the next day.
2. Taper and immediate switch: The current antidepressant is tapered down gradually, and the new antidepressant is initiated as soon as the current antidepressant is discontinued completely.
3. Taper and switch after washout: The current antidepressant is tapered down gradually, and the new antidepressant is initiated after a washout period of 1 to 6 weeks (depending on the half-life of the drug being discontinued), during which time the patient takes no antidepressant medication.
4. Cross tapering: The dose of the current antidepressant is gradually tapered down while the dose of the new antidepressant is gradually tapered up.
Selecting a switching strategy depends on multiple factors. Notably, when switching from one antidepressant to another that has potentially dangerous drug-drug interactions (e.g., when switching to or from a non-selective, irreversible monoamine oxidase inhibitor such as phenelzine or tranylcypromine), the taper and switch after washout strategy should always be employed.3

Cross tapering is a useful strategy when there is concern about drug-drug interactions, but it is not deemed advisable to have patients unmedicated for any period of time. It should be noted, however, that co-administration of certain antidepressants is absolutely contraindicated. This includes the combination of clomipramine with selective serotonin reuptake inhibitors (SSRIs), venlafaxine, or duloxetine as well as the combination of agomelatine and fluvoxamine. Cross tapering of SSRIs and tricyclic antidepressants should also be done with extreme caution.3
Cross tapering can additionally be used to minimize discontinuation symptoms from the initial antidepressant as well as short-term tolerability problems with the new antidepressant. For this reason, patients known to be sensitive to drug side effects may benefit from this approach.

When switching between two antidepressants with a similar mode of action, a direct switch can often be safely employed. The one exception to this rule is switching from fluoxetine to another SSRI antidepressant. Because of the long half-life of fluoxetine, a gap of 4 to 7 days between antidepressants is recommended.3

If there is concern about discontinuation symptoms, particularly in patients who have been taking the current antidepressant for a long period of time, the taper and immediate switch can be used as an alternative to the direct switch. The taper and immediate switch approach can also be used when switching from one SSRI antidepressant to another, in order to avoid any risk of serotonin syndrome, or when switching from duloxetine to an SSRI or venlafaxine.3

There is considerable information to help guide clinicians when switching between two specific antidepressants. Clinicians can access this information through resources available online, including SwitchRx.ca and an antidepressant switch table compiled by BC Guidelines as part of their 2013 Guidelines entitled Major Depressive Disorders in Adults (Appendix D), available at http://www2.gov.bc.ca/assets/gov/health/practitioner-pro/bc-guidelines/depress_appd.pdf.

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